A Randomized Placebo-Controlled Trial of Secukinumab on Aortic Vascular Inflammation in Moderate-to-Severe Plaque Psoriasis (VIP-S)

Abstract

Psoriasis, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18 F-2-fluorodeoxyglucoseepositron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n [ 46) versus placebo (n [ 45) was e0.053 (95% confidence interval ¼ e0.169 to 0.064; P [ 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-a (P [ 0.0063) and ferritin (P [ 0.0354), and an increase in fetuin-A (P [ 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.

Addressing Hypertension in Patients With Psoriasis: Review and Recommendations

“…Recent clinical trials, including the Vascular Inflammation in Psoriasis Trial on ustekinumab's effect on vascular inflammation, may provide some insights in post hoc analyses. 76,77…”

T Cells in Autoimmunity-Associated Cardiovascular Diseases

“…Because CVD is a major cause of morbidity and mortality in patients with systemic autoimmunity, targeting the immunologic drivers of vascular inflammation has the potential to substantially improve the quality of life of these individuals ( 78 , 92 , 113 ). Investigating the mechanisms of T-cell-mediated CVD in psoriasis has already culminated in late phase clinical trials, with additional studies ongoing ( 18 , 20 , 21 ). Ongoing investigations into the mechanisms by which T cell cells promote autoimmunity-related CVD will uncover additional therapeutic targets, allowing a more sophisticated approach to preventing and treating CVD in these cohorts.…”

“…Tumor necrosis factor (TNF) inhibitors, IL-6 receptor inhibitors, and JAK inhibitors all inhibit multiple immune subsets, including pathogenic T cells; these agents are all associated with reduced markers of CVD in patients with systemic autoimmunity (80,126,128,133,134). Biological DMARDs can also block T-cell-derived factors: as noted previously, blockade of Th17-derived IL-17A may ameliorate CVD in psoriasis, although further studies are needed (18,19,21,97). Finally, the biological DMARD abatacept, which is FDAapproved for RA and psoriatic arthritis, directly targets T cell activation by blocking costimulation.…”

“…Subsequently, a number of late phase clinical trials tested the effects of blocking IL-17A and IL-23 on aortic vascular inflammation in patients with psoriasis. Although the immunomodulatory treatments caused transient improvements in inflammation, these changes were not sustained ( 20 , 21 , 92 ). This may be due to the role of other T helper subsets in psoriatic CVD, or because these large studies evaluated aortic inflammation instead of a more sensitive primary outcome measure such as coronary artery plaque burden.…”

“…Furthermore, CV risk is reduced in patients with rheumatic diseases who achieve clinical remission. This observation has led to multiple studies testing the efficacy of anti-inflammatory therapies as a primary prevention strategy for CVD in patients with autoimmune disease (17)(18)(19)(20)(21). In order to select the most promising therapeutic targets, it is critical to understand the specific mechanisms by which T cells interact with other dysregulated populations to promote CVD in patients with autoimmunity.…”